Subgroup Analyses from Randomized Phase 3 Study of Atezolizumab vs Docetaxel in Patients with Advanced NSCLC (OAK)
The OAK trial compared atezolizumab with docetaxel in patients with previously treated non–small-cell lung cancer (NSCLC). Safety and efficacy data for the intent-to-treat (ITT) population were presented at the European Society for Medical Oncology (ESMO) Congress in October 2016. During WCLC, researchers presented subgroup analyses based on PD-L1 expression, histology, central nervous system (CNS) metastases (mets), tobacco use, and EGFR mutation status.
The 1225 patients with previously treated NSCLC who enrolled in OAK were stratified according to PD-L1 status, number of prior chemotherapy regimens, and histology. Patients received atezolizumab (1200 mg IV every 3 weeks) or docetaxel (75 mg/m2 IV every 3 weeks). Data from 850 patients that were presented at ESMO showed a 27% improvement in overall survival (OS) in patients receiving atezolizumab versus docetaxel (P =0.0003), regardless of PD-L1 expression levels and including patients with PD-L1 expression of <1%.
The WCLC update confirmed that an OS benefit was seen in patients with low or no PD-L1 expression (12.6 months [atezolizumab] vs 8.9 months [docetaxel]; hazard ratio [HR], 0.75), based on both immunohistochemistry and gene expression.
OS was also significantly improved for atezolizumab versus docetaxel regardless of histology. Median OS among patients with nonsquamous NSCLC was 15.6 versus 11.2 months, respectively (HR, 0.73). Median OS among those with squamous NSCLC was 8.9 versus 7.7 months, respectively (HR, 0.73).
When comparing azetolizumab with docetaxel in 85 patients with CNS mets, the HR for OS was 0.54. Among 765 patients without CNS mets, the HR for OS was 0.75. Although the rate of new CNS mets was similar overall, time to development of new CNS mets was longer in patients receiving atezolizumab.
Researchers concluded that atezolizumab demonstrated broad efficacy in all tested subgroups, with the exception of patients with EGFR mutations. Similar to other checkpoint inhibitors, no improvement in OS was seen for atezolizumab in patients with EGFR mutations.
Gadgeel S, et al. WCLC 2016. Abstract PL 04a.02. ID 5822.